Lintuzumab Ac225 for Myelodysplastic Syndrome

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, Investigational agents

Disqualifiers: CNS leukemia, Active GVHD, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to determine the safest dose and assess the side effects of a new treatment called lintuzumab-Ac225 for individuals with high-risk myelodysplastic syndrome (MDS) that has not responded to previous treatments. Lintuzumab-Ac225 combines a monoclonal antibody, which attaches to cancer cells, with a radioactive agent to target and kill these cells. This trial may suit those diagnosed with MDS who have not improved after medications like azacitidine or decitabine and whose cancer cells display a specific marker called CD33. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you are on other investigational agents or therapies that could increase toxicity or interfere with the study within the last 30 days before enrollment.

Is there any evidence suggesting that lintuzumab-ac225 is likely to be safe for humans?

Research shows that lintuzumab-Ac225, a treatment for high-risk myelodysplastic syndrome, remains in the early testing stages to assess its safety for humans. Earlier studies found some side effects, primarily affecting blood cells, which was expected since many patients had already undergone extensive treatment. Despite these side effects, the treatment maintains a manageable safety profile, with no early deaths reported in the first 30 days of treatment. The maximum tolerated dose, which causes the most side effects, has not yet been determined, indicating that higher doses might still be tested. This treatment targets specific cancer cells and delivers a radioactive agent to kill them, making it a potentially promising option. However, further research is needed to fully understand its safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Myelodysplastic Syndrome, which often involve chemotherapy or blood transfusions, Lintuzumab Ac225 is unique because it targets cancer cells directly with a radioactive isotope. This treatment combines an antibody, lintuzumab, with Actinium-225, a radioactive element that delivers targeted radiation to the cancer cells. Researchers are excited about this approach because it has the potential to limit damage to healthy cells, possibly leading to fewer side effects and improved outcomes for patients.

What evidence suggests that lintuzumab-ac225 might be an effective treatment for myelodysplastic syndrome?

Research has shown that lintuzumab-Ac225, the treatment under study in this trial, may effectively treat blood cancers such as acute myeloid leukemia (AML) and myelodysplastic syndrome. In previous studies, 42% of high-risk patients achieved a complete response, with their cancer becoming undetectable. The treatment also benefited over half of the patients, with an overall response rate of 58%. Lintuzumab-Ac225 targets specific cancer cells and delivers a radioactive substance to destroy them. Early results indicate a manageable safety profile, as it does not cause severe side effects for most people. While further research is necessary, these findings offer hope for those with high-risk, hard-to-treat myelodysplastic syndrome. ^{1 4 5 6 7}

Who Is on the Research Team?

Talha Badar

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for patients with high-risk myelodysplastic syndrome (MDS) that hasn't improved after treatment with azacitidine or decitabine. Participants must have a confirmed MDS diagnosis, CD33 positive myeloblasts, be relatively active (ECOG ≤ 2), and have normal organ function tests. HIV-positive patients can join if they're on effective therapy.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

My direct bilirubin levels are within normal range.

My MDS condition shows more than 5% myeloblasts.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive lintuzumab-ac225 IV, over 30 minutes, on day 1 of each cycle. Cycles repeat every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

16 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Lintuzumab Ac225

Trial Overview The trial is testing Lintuzumab Ac225, a radioactive immunotherapy targeting CD33 positive cancer cells in MDS patients who haven't responded to other treatments. It's a phase I study to determine the safety and optimal dose of this new potential treatment.

How Is the Trial Designed?

Group I: Treatment (lintuzumab-ac225) Experimental Treatment 5 Interventions

Patients receive lintuzumab-ac225 IV, over 30 minutes, on day 1 of each cycle. Cycles repeat every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo SPECT/CT scans and buccal swab on study, as well as bone marrow aspiration throughout the trial.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06888323

Study Details | NCT06888323 | Testing an Anti-cancer ... Giving lintuzumab-ac225 may be safe, tolerable and/or effective in treating patients with high risk, refractory myelodysplastic syndrome. Detailed Description.

2. bloodcancerstoday.com bloodcancerstoday.com/post/novel-radiotherapy-offers-strong-aml-combo-therapy-backbone

Novel Radiotherapy Offers Strong AML Combo Therapy ... Lintuzumab-Ac-225 (Actimab-A) shows promise as a treatment backbone for relapsed or refractory acute myeloid leukemia (AML), according to a press release.

3. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/1539/499833/Updated-Results-from-Phase-1-Study-of-Targeted

Updated Results from Phase 1 Study of Targeted ... The combination of lintuzumab-Ac225 and venetoclax had a manageable safety profile and no early mortality at day 30. The MTD was not reached and ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39955432/

Phase 1 study of lintuzumab-Ac225 combined with CLAG ... Measurable residual disease (MRD)-negativity was achieved in 8 of 12 responders. Among all patients (n = 26), estimated 2-year OS was 23.1% (95% CI, 9.4-40.3) ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e19030

Sequential salvage chemotherapy and lintuzumab-Ac225 ... In high-risk pts, 42% (n=8) of pts achieved CRc (CR+CRi), 16% (n=3) achieved MLFS, for an overall response rate (ORR) of 58%. Among evaluable ...

6. trialx.com trialx.com/clinical-trials/listings/303013/testing-an-anti-cancer-radio-active-immunotherapy-called-lintuzumab-ac225-in-patients-with-high-risk-myelodysplastic-syndrome-that-has-not-responded-to-other-treatment/

Testing an Anti-cancer Radio-Active Immunotherapy ... Giving lintuzumab-ac225 may be safe, tolerable and/or effective in treating patients with high risk, refractory myelodysplastic syndrome.

7. jnm.snmjournals.org jnm.snmjournals.org/content/65/supplement_2/241340

Safety and Dosimetric Analysis of Lintuzumab-Ac225 in ... Among all patients, Grade 3/4 toxicities observed in >10% of patients included hematologic toxicities, as expected for heavily pre-treated ...